Cytoplasmic p63 immunohistochemistry is a useful marker for muscle differentiation: an immunohistochemical and immunoelectron microscopic study

TP63, a member of the TP53 gene family, is a nuclear marker of myoepithelial cells. Antibody against p63 is frequently used to aid in the diagnosis of prostate carcinoma, as well as in the identification of myoepithelial cells in other tissues including the breast. p63 is also a marker for squamous cell carcinoma. Recently, it was found that all p53 family members are involved in regulating the process of muscle differentiation through the retinoblastoma (RB) protein. Ablation of these p53 family functions blocks the differentiation program and promotes malignant transformation by enabling cooperating oncogenes to transform myoblasts. We therefore studied p63 expression in a number of neoplasms with myogenic differentiation. Immunohistochemical staining for p63 was performed on paraffin sections from 38 rhabdomyosarcomas, five leiomyomas, five leiomyosarcomas, five rhabdomyomas, five rhabdomyomatous Wilms tumors, three normal cardiac muscles, one medullomyoblastoma, one pleuropulmonary blastoma with rhabdomyomatous differentiation, and one teratoma with prominent rhabdomyoblasts. Each case was also stained with desmin. Unlike the nuclear staining scored in myoepithelial cells, only cytoplasmic staining for p63 was considered positive. Of 38 cases of rhabdomyosarcoma, 36 showed cytoplasmic p63 staining; 24 of these showed highlighting of cross-striations superior to that of desmin. In addition, 5/5 rhabdomyomas, 5/5 rhabdomyomatous Wilms tumors, 1/1 pleuropulmonary blastoma with rhabdomyomatous differentiation, 1/1 teratoma with atypical rhabdoblasts, and 1/1 medullomyoblastoma exhibited cytoplasmic p63 staining. Normal cardiac muscle samples (3/3) also demonstrated positive cytoplasmic staining and distinct cross-striations. Smooth muscle tumors exhibited only very focal and faint cytoplasmic staining in 5/5 leiomyomas and 4/5 leiomyosarcomas. Immunoelectron microscopic study of skeletal muscle showed p63 localization to the Z bands of sarcomeres. We conclude that p63 immunostain is a sensitive marker for skeletal muscle differentiation and highlights the cross-striations of strap cells with exceptional definition. Modern Pathology (2011) 24, 1320-1326; doi:10.1038/modpathol.2011.89; published online 27 May 2011